title: Retargeting T cells for HER2-positive tumor killing by a bispecific Fv-Fc antibody.
abstract: To exploit the biological and pharmacological properties of immunoglobulin constant domain Fc fragment and increase the killing efficacy of T cells, a single chain variable fragment specific to CD3 was fused with Fcab (Fc antigen binding), a mutant Fc fragment with specificity against Human epidermal growth factor receptor 2 (HER2) developed by F-star. The bispecific fusion named as FcabCD3 was expressed by transient transfection in HEK-293T cells and purified by affinity chromatography. Specific cytolytic activity of retargeted T cells to kill HER2 positive SKBR3 cell line was evaluated in vitro. FcabCD3 was able to retarget T cells to kill both Herceptin insensitive Colo205-luc cell line and HER2 low expression MDA-MB-231-luc cell line. Furthermore, FcabCD3 was effective in eliminating the Colo205 tumor established on BALB/c nu/nu mice.
authors.affiliation: Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), Institute of Microbiology, Chinese Academy of Sciences, Beijing, China ; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Yanran
authors.initials: Y
authors.lastname: He
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Ma
authors.forename: Changzhen
authors.initials: C
authors.lastname: Liu
authors.forename: Wen
authors.initials: W
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Huamin
authors.initials: H
authors.lastname: Han
authors.forename: Bhargavi M
authors.initials: BM
authors.lastname: Boruah
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology*; D017252:CD3 Complex / Q000235:genetics* / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics* / Q000276:immunology*; D020014:K562 Cells; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018033:Antibodies, Bispecific; D017252:CD3 Complex; D007141:Immunoglobulin Fc Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; C508053:ERBB2 protein, human